I say pay a little extra and stay on the strip. If you don't, you'll end up dropping serious coin on cab rides.
My advice:
Stay away from the Stratosphere end (Circus Circus, Hilton, Sahara)
For medium price/quality, Planet Hollywood is a great deal
I agree with a previous post, if you can get a good deal, the Venetian is excellent
Excalibur, Luxor and Imperial Palace = Harvey Updyke
Ceasar's palace is kinda overpriced for what you get
Palms = played out Jersey shore crowd (but the view from the Ghost Bar and Playboy club are amazing)
Freemont Street (Binions, Golden Nugget) = Cheap tables, but no upscale experience
Make sure you take shoes that you have broken in, because even though the next casino is only a block away, the scale of the buildings is so large, nothing is a short walk. If your wife wears heals out, she should probably drop some flats in her purse (or your night will be cut short)
My vote = Venetian or if on a budget, Planet Hollywood